Background: Latinos are the largest and fastest growing minority group (16% of the US population) and provide a potent example of existing health disparities among U.S. racial/ethnic groups. In particular, Mexican Americans-the largest US Latino subpopulation-have a notably higher prevalence of overweight and obesity (80%) than non-Hispanic whites (NHWs, 68%), and they are disproportionately affected by obesity-related risk factors (e.g., metabolic syndrome, pre-diabetes) and diseases (e.g., diabetes). Until efficacious lifestyle interventions for weight management are translated into practice, obesity and its comorbidities will continue to exact enormous and disproportionate burdens. Population-specific interventions are needed because undifferentiated interventions (often developed in white-dominant populations) may be inefficient-or even unintentionally increase health disparities. The Diabetes Prevention Program (DPP) trial demonstrated that an intensive lifestyle intervention reduced type 2 diabetes incidence by 58% among high-risk adults and that weight loss was the dominant predictor. Numerous DPP translation studies have been undertaken, including a pragmatic randomized trial our team recently completed (E-LITE) with 241 participants (78% NHW) that showed success in integrating group counseling with health information technology (HIT) to operationalize the DPP intervention in primary care. To date, very few DPP translation studies have targeted Latinos. Design: We propose to culturally adapt the IT-enhanced group DPP intervention from E-LITE and test it among Spanish-speaking or bilingual Mexican Americans who are overweight or obese and have metabolic syndrome, pre-diabetes, or both. Participants (n=186) from 6 primary care practices in Santa Cruz, California (35% Latino residents; 91% of Mexican origin) will be randomly assigned to receive the culturally adapted intervention (CAI) or usual care. The primary aim is to determine the effectiveness of the CAI (E in the RE-AIM model). We hypothesize that the CAI will lead to a greater mean reduction in body mass index at 24 months (primary outcome) vs. usual care. Secondary outcomes will include cost-effectiveness, clinical (e.g., fasting glucose), psychosocial (e.g., quality of life), behavior change (e.g., diet, physical activity) measures. The secondary ai is to conduct process evaluation with mixed methods for the other RE-AIM attributes: Reach (e.g., participation rate of the target population), Adoption (e.g., participating clinic & provide characteristics), Implementation (e.g., intervention fidelity), and Maintenance (e.g., sustainabiliy in the practice setting). Implications: This health services research project (PA-13-045) falls within the AHRQ Research Portfolio areas of comparative effectiveness, HIT, and prevention and care management; it also targets a priority population. The findings will be of value to clinicians, patients, and other decision makers considering effective obesity and diabetes prevention programs for the millions of MAs who carry a disproportionate burden of these, with high potential for real-world applicability and impact on MA minority health and policies aimed to eliminate health disparities.